Synthesis and biological evaluation of 4-phenoxy-6,7-disubstituted quinolines possessing semicarbazone scaffolds as selective c-Met inhibitors.

Novel quinoline derivatives bearing acyclic semicarbazones were prepared and their chemical structures as well as the relative stereochemistry were confirmed. All the synthesized compounds were evaluated for their c-Met kinase inhibitory activity and their cytotoxicity against the cell lines HT-29, MKN-45, and MDA-MB-231 in vitro. Several potent compounds were further evaluated against A549 cells. Most compounds displayed moderate to excellent activity, and the structure-activity relationship studies identified the most promising compound 35 as a selective c-Met kinase inhibitor (IC50 = 4.3 nM). Compound 35 showed a 3.5- and 18.8-fold increase in cytotoxicity in vitro against HT-29 and A549 cells, respectively, compared to that of foretinib. Poor off-target effects of compound 35 were further confirmed by the antiproliferative activity against the c-Met inhibition less sensitive MDA-MB-231 cell line (IC50 = 0.77 µM).

The principle and effect of transfer agent for the removal of PCE during in situ chemical oxidation.

Viscosity remedial technology, which uses a water-soluble polymer mixed with remedial fluids, has been introduced in recent years to improve the removal efficacy of perchloroethylene/tetrachloroethylene (PCE) by improving oxidant coverage (i.e. sweep efficiency). Xanthan gum and hydrolysed polyacrylamide (HPAM) are relatively stable with time and temperature and possess salt and oxidation resistance, indicating that they may be good flooding agents (the former is better than the latter in this work). In this work, we quantified the polymer directly improved oxidation of PCE during transport by using a two-dimensional flow tank. Using a low pore volume (≤3.0), the removal rate of the PCE increased with the polymer concentration before stabilizing at approximately 93.00 and 88.30% for xanthan and HPAM, respectively. In this work, over 80% of PCE was removed via less than 3.0 PV of the SDS solution, whereas complete removal (100%) was achieved with less than 3.0 PV of SDS foam. Furthermore, the new experimental discoveries demonstrate that xanthan is better than HPAM and SDS foam is a better remediation agent than the SDS solution for removing PCE. Graphical abstract (Reaction device, A - inlet device (pump 1#), B - 2D tank, C - outflow device (pump 2#), D - data recording and processing device, E - microscopic expression, E (a) - KMnO4 flushing, E (b) - polymer solution flushing).

Farmland-atmosphere feedbacks amplify decreases in diffuse nitrogen pollution in a freeze-thaw agricultural area under climate warming conditions.

Although climate warming and agricultural land use changes are two of the primary instigators of increased diffuse pollution, they are usually considered separately or additively. This likely lead to poor decisions regarding climate adaptation. Climate warming and farmland responses have synergistic consequences for diffuse nitrogen pollution, which are hypothesized to present different spatio-temporal patterns. In this study, we propose a modeling framework to simulate the synergistic impacts of climate warming and warming-induced farmland shifts on diffuse pollution. Active accumulated temperature response for latitudinal and altitudinal directions was predicted based on a simple agro-climate model under different temperature increments (△T0 is from 0.8°C to 1.4°C at an interval of 0.2°C). Spatial distributions of dryland shift to paddy land were determined by considering accumulated temperature. Different temperature increments and crop distributions were inserted into Soil and Water Assessment Tool model, which quantified the spatio-temporal changes of nitrogen. Warming led to a decrease of the annual total nitrogen loading (2.6%-14.2%) in the low latitudes compared with baseline, which was larger than the decrease (0.8%-6.2%) in the high latitudes. The synergistic impacts amplified the decrease of the loading in the low and high latitudes at the sub-basin scale. Warming led to a decrease of the loading at a rate of 0.35kg/ha/°C, which was lower than the synergistic impacts (3.67kg/ha/°C) at the watershed level. However, warming led to the slight increase of the annual averaged NO3 (LAT) (0.16kg/ha/°C), which was amplified by the synergistic impacts (0.22kg/ha/°C). Expansion of paddy fields led to a decrease in the monthly total nitrogen loading throughout the year, but amplified an increase in the loading in August and September. The decreased response in spatio-temporal nitrogen patterns is substantially amplified by farmland-atmosphere feedbacks associated with farmland shifts in response to warming.